N-(1-halo-1-nitroalkylthio)dicarboximides



United States Patent 3,468,905 N-(l-HALO-l-NITRGALKYLTHIO) DICARBOXTMIDES Gustave K. Kohn and Joseph G. E. Fenyes, Berkeley, Calif., assignors to Chevron Research Company, San

Francisco, Calif., a corporation of Delaware No Drawing. Filed Sept. 7, 1965, Ser. No. 485,619 Int. Cl. (3076 51/32, 49/32, 27/06 US. Cl. 260-326 3 Claims ABSTRACT OF Tim DISCLOSURE N-(l-halo-l-nitroalkylthio) dicarboximides wherein the alkyl group contains 2 to 6 carbon atoms and the halogen is of atomic number 17 to 35. Typical dicarboximides are N-(l-chloro-l-nitroethylthio) phthalimide, N-(l-halo-lnitropropylthio) 5,5 dimethyl hydantoin, N,N-di-(lchloro-l-nitropropylthio) uracil and 1,1-bis-(chloro-1-nitropropylthio) parabanic acid. These carboximides are fungicidal.

wherein A- is one of the following groups:

(1) 1,2-hexacarbocyclic group having from 0-3 sites of olefinic (aromatic) unsaturation;

wherein R is hydrogen or lower alkyl of from 1 to 6 carbons;

wherein R is hydrogen or lower alkyl, i.e., from 1 to 6 carbons, and B is a l-halo-l-nitroalkyl group in which the halogen is of atomic number 17 to 35 and the alkyl is of from 2 to 6 carbons, i.e., ethyl through hcxyl.

The compounds in which A is hexacarbocyclic may be more explicitly described by the formula:

3,468,905 Patented Sept. 23, 1969 wherein X is halogen of atomic number 17 to 35, R is alkyl of from 1 to 5 carbons and the LZ-cyclohexylene ring has from 0 to 3 sites of olefinic unsaturation, i.e., 1,2- phenylene, 1,2-dihydropheny1ene, 1,2-tetrahydrophenylene and 1,2-hexahydrophenylene. Alternatively, the ring may be considered as phthalimide and derivatives thereof. In this case the ring could be phthalimide, dihydrophthalimide, tetrahydrophthalimide and hexahydrophthalimide. The ring may be unsubstituted or singly substituted with a chloro, bromo, nitro or alkyl group such as methyl, ethyl, butyl, amyl, etc.

The dihydro derivatives, that is, dihydrophthalimide, may be 1,3-, 1,4-, 2,4-, 3,5-, etc. The tetrahydro derivative may be 1-, 2-, 3-, or 4. Preferred compounds are phthalimide and A -tetrahydrophthalimide.

Specific illustration of hexacarboxylic compounds included Within the above formula are:

N- l-chloro-l-nitroethylthio -phthalimide,

N-( l-bromol-nitrobutylthio -phthalimide,

N-( l-chloro-1-nitropr0py1thio -1,3-dihydrophthalimide,

N-( l-bromo-l-nitrohexylthio-1,4-dihydrophthalimide,

N (l-chloro-l-nitroamylthio) cis-A -tetrahydrophthah imide,

N (l-chloro-l-nitroethylthio) cis-u -tetrahydrophthalimide,

N-( l-bromo-l-nitropropylthio) -3,5-dihydrophthal imide,

N (1-bromo-1-nitrobutylthio) cyclohexane-1,2-dicarboximide,

N (l-bromo-l-nitroethylthio) cyclohexane-LZ-dicarboximide,

4-uitro-N- l-chloro-l-nitrobutylthio) -phthalimide,

3 methyl N-(l-bromo-l-nitroethylthio)-cyclohexane- 1,2-dicarboximide,

4-chloro-N-( l-bromo-l-nitropropylthio) -phthalimide,

3 bromo N-(l-chloro-l-nitroamylthio)-cis-A -tetrahydrophthalimide, etc.

The hydantoin compounds of this invention may be more rigorously represented by the formula wherein X is halogen of atomic number 17 to 35, i.e., chlorine or bromine, R is alkyl of from 1 to 5 carbons and R is hydrogen or lower alkyl. Included among the lower alkyl groups are, methyl, ethyl, propyl, butyl, amyl and hexyl. Preferred compounds are the 3-(1-halo-1-nitroalkyl) hydantoins.

Illustrative examples of some of the hydantoin compounds included in this invention are: 3-(1-chloro-1-nitroethylthio) hydantoin, 3-(l-bromo-l-nitrobutylthio) hydantoin, 3-(l-chloro-l-nitrohexylthio) hydantoin, 3-(1- chloro l-nitropropylthio)-5,5-dimethylhydantoin, 3-(1- bromo-l-nitroamylthio -5-methylhydantoin, 3-(l-ch1oro- 1 nitroethylthio)-5-ethylhydantoin, 3-(1-chloro-1-nitrobutylthio) 5 butylhydantoin, 3-(1-bromo-lnitroethylthio)5,5-dipropylhydantoin, etc.

Also, the pyrimidine compounds of this invention may be further defined by the structure R (E-C N02 I HO N-S-G-R N-G N02 I I] l 0 wherein X is halogen of atomic number 17 to 35, R is alkyl' of from 1 to 6 carbons and R is hydrogen or methyl. As derivatives of pyrimidine, these compounds may be termed 2,6 dioxypyrimidine or methyl-dioxypyrimidine, i.e., uracil or thymine.

Illustrative of the compounds in this grouping are: N,N di (l-chloro-l-nitroethylthio) uracil, N,N-di=(1- bromo-l-nitrobutylthio) uracil, N,N-di-(l-chloro-l-nitrohexylthio) uracil, N,N di-(l-bromo-l-nitropropylthio) thymine, N,N di (1 chloro-l-nitroethylthio) thymine, N,N-di-(1-chloro-l-nitrohexylthio) thymine, etc.

Examples of the di-( l-halo-l-nitroalkylthio) substituted parabanic acids of this invention are 1,3-bis-(1-chloro-1- nitroethylthio) parahanic acid, 1,3-bis-(1-bromo-l-nitrobutylthio) parabanic acid, l,3-bis-(l-chloro-l-nitrohexylthio) parabanic acid, etc.

The preparation of the unique N-(l-halo-l-nitroalkyl) dicar-boximides of this invention may be carried out by reacting an alkali metal salt of the corresponding imide with a l-halo-l-nitroalkylsulfenyl halide. The imide may be contained in a suitable inert medium, such as an aromatic solvent, e.g., benzene, toluene, etc., an alcohol, e.g., methanol, ethanol, etc. or water. Furthermore, the imide may be used directly in the form of its alkali metal salt or the salt may be formed in situ.

The solution or suspension of the alkali metal salt of the imide is vigorously stirred, preferably at low temperature while the sulfenyl halide is added. The sulfenyl halide may be contained in a suitable inert solvent, such as petroleum ether or mixed hexanes, if desired. After a sufiicient reaction period the product is isolated by fitlration or by stripping off the solvent. The product then may, if desired, be recrystallized from a suitable solvent, such as methanol or an aromatic solvent.

The l-halo-l-nitroalkylsulfenyl halides used in the preparation of the compounds of this invention may he synthesized by reacting an alkali or alkaline earth metal salt of a primary nitroalkane with sulfur monochloride in the presence of an anhydrous, nonhydroxylic inert medium, such as ether, to form a bis-(l-nitroalkyl) disulfide and cleaving the disulfide with halogen, i.e., chlorine or bromine.

In specific illustration of the compounds of this invention and their method of preparation, the following examples are presented. These examples are ofiFered as representative of the compounds falling within the scope of this invention and are not intended as limiting of the invention herein described.

EXAMPLE I A 4.2, m.-portion of the potassium salt of phthalimide mixed Wlth 50 mls. ether was charged to a vessel. To this mixture was added 4.0 gm. l-chloro-l-nitroethylsulfenyl chloride in ether. This mixture was stirred for 15 minutes after which the solids were filtered from the mixture. The solids were washed with water and dried, to leave 3 gms. N-( l-chloro-l-nitroethylthio) phthalimide. This compound was observed as a white solid which melted at 110- 112 C. Its analysis was: percent CI: theory12.4, found12.28; percent S: theoryl1.l5, fund11.15.

EXAMPLE H A 5.0 gm.-portion of the sodium "salt of cis-A -tetrahydrophthalimide was charged to a vessel. To this mixture was added 5.45 gm. l-chloro-l-nitropropylsulfenyl chloride in ether. The contents were stirred overnight and then filtered. The solids were washed with water and hexane and then dried. The product, N-(l-chloro-l-nitropropylthio)-cis-A -tetrahydrophthalimide, was observed as a. solid which melted at 104-405 (3. Its anlysis was: percent Cl: theory-11.64, foundl1.68; percent S: theory 10.52, foundl0.30.

Using the methods described in Examples I and II, various other 1,2-hexacarbocyclic dicarboximides were prepared. The analyses of these compounds are contained in Table I.

TABLE I Analyses Percent 01 Percent S Compound Theory Found Theory Found N-(1-chloro l-nitropropylthio) phthalimide ll. 78 11. 0 10. 66 10. 22 N-(l-chloro-l-nitroethylthio)-cis- M-tetrahydrophthalmide 12. 54 12. 65 11. 02 10. 65

EXAMPLE III A 3.0 gm.-portion of the monopotassium salt of hydantoin in ether was charged to a vessel. To this suspension 3.75 gm. l-chloro-l-nitropropylsulfenyl chloride were added. The contents were stirred for 1 hour and allowed to stand for 3 days. The mixture was filtered and the solids were slurried with water. The Water slurry was filtered and the solids were dried leaving 3.2 gms. 3-(1-chloro-l-nitropropylthio) hydantoin. It was observed as a white solid which melted at l57l 60 C. with decomposition. Its analysis was: percent Cl: theory-14.0, found 14.33; percent S: theory-12.65, foundl2.20.

EXAMPLE IV EXAMPLE V In the manner described in Example IV, N,N-di-( l-chloro-l-nitroethylthio) uracil was prepared. It melted at 146 C. with decomposition and had the following analysis: percent Cl: theory-19.12, found18.'63; percent S: theory-16.4, found15.51.

EXAMPLE VI A 5 .0 gm.-portion of the dipotassium salt of parabanic acid dissolved in ether Was charged to a vessel. To this mixture was added 10.0 gm. l-chloro-l-nitropropylsulfenyl chloride. The contents were stirred for 1 hour and allowed to stand for 3 days. The solids were filtered off and the ether was stripped from the filtrate. The stripped filtrate was further distilled to 60 C. at 1.0 mm. Hg to give 4 gms. 1,3-di-(1-chloro-l-nitropropylthio) parabanic acid. This product was observed to be a viscous orange oil.

These new compounds find use in the control and killing of fungi. A number of the invention compounds were evaluated for fungicidal elfectiveness by means of the mycelial drop test. This test is designed to measure the fungitoxic activity of fungicidal chemicals in terms of their degree of inhibition upon mycelial growth. Each compound to be tested was dissolved in acetone in dilutions as indicated in Table II. Paper discs previously inoculated by impregnation with equal amounts of particular fungus mycelium placed on potato dextrose agar medium were treated by applying a precise and equal volume of each of these fungicidal solutions to their center. Following treatment with the fungitoxic chemical, the discs were incubated along with inoculated but untreated control discs at ambient temperatures until such time that these untreated control discs were filled with mycelial growth. Activity of the fungitoxic chemical tested was determined by comparative measurements of radii of mycelial growth away from the edge of the disc in treated and untreated samples. From this comparison a percent inhibition of growth area was determined. The results of this test for various compounds of this invention on the particular fungus mycelium are indicated in Table II.

lesions on the primary leaves. These counts were compared with a similarly inoculated but unsprayed control series to determine the percentage of fungus control TABLE II Fungus Myeellim Percent Inhibition Concentration, Pyth- Fusar- Rhi- Verti- Compound p.p.In. .l imn ium zoctonia cilliurn N-(1-chloro-l-nitroethylthio)phthalimide 500 N-(l-chloro-l-nitropropylthio) phthalimide 500 97 N-(l-chlorol-nitropropylthio) cis-M-tetrabydrophthalim 500 100 N-(l-chlortH-nitroethylthio)-cis-N-tetrahydrophthalimide 500 100 3-(Lchlorou-nitropropylthio) hydantoin 500 100 N,N-di-(l'chloral-nitropropylthio) uracil 500 100 l,3-di-(l-chlortrl nitropropylthio) parabani 500 100 50 70 A number of the compounds were also tested for effectiveness against spores by means of The Standard Spore Slide-Germination Method for Determining Fungicidal Activity, described in the American Phytopathological Society Journal, volume 33, pages 627-632, (1943). The method is designed to measure the fungitoxic activity of fungicidal chemicals, their activity being expressed in terms of percent inhibition of germination of fungus spores.

Each compound to be tested was dissolved in acetone to a concentration of 10 ppm. These solution were then pipetted into the wells of depression slides and allowed to dry. The wells were filled with a spore suspension of the specified test organism and incubated in a moist chamber overnight. A group of 100 spores was examined and the number of spores germinated and not germinated Was effected by the fungitoxic chemical. The results appear in Table IV.

TABLE IV.-IN VIVO, BEAN RUST counted and recorded to show the biological activity in terms of the percentage germination inhibition. Table 111 reports the results of this testing.

TABLEZIII Organism Percent Inhibition l lonoli'nia Altemtm'q Fuson'unr Compound fructz'cola solam aolam N-(l-chloro-l-nitroethylthio) phthalimide 98 100 N-(1-chloro-l-nitropropylthio) phthalimide 100 61 N-(l-chloro-l-nitropropylthio)-cis-A -tetrahydro phthalimide 70 97 N-(l-chloro-l-nitroethylthio)-cis-A -tetrahydrophthalimide 97 100 3-(1-chlot'o-l-uitropropylthio) hydantoin 30 "1.66

N,N-di-(1-ch1orol-nitropropylthi0) uracil Additionally, a similar sampling of the compounds of this invention were tested for fungicidal activity in vivo. In these tests, the chemicals were tested for the control of bean rust. According to this procedure, thre replicate pinto bean plants growing in a standard University of California soil mix, in the 3-triplicate state and approximately 5 inches tall were sprayed at 15 psi. with an acetone solution of each of the compounds to be tested at a concentration of 500 ppm. These suspension made uniform by means of an inert wetting agent and suitable filler. The plants were dried at ambient greenhouse temperatures and then inoculated with a spray of approximately 30,000 urediospores per mil. of Uromeyces phasecoli zypica, the fungus causing bean rust. The plants were immediately incubated in a moist room for 24 hours at 7273 F. and a relative humidity of 99-97%, after which they were removed to a room with ambient temperatures in the range of 7580 F. and a relative humidity of 85-90% for 12 days. At the end of this incubation period, disease readings were mad by counting the local Aside from the specific formulation and application of the class of compounds of the invention as represented by the foregoing tests, these compounds may be dispersed in or upon other inert liquid and solid carriers, such as inert clay, xylenes, etc. The solid carriers may be in the form of a dust, or used in conjunction with a suitable wetting agent to form a wettable powder. The fungi-toxic compounds of the invention may also be formulated with other solvent, dispersing agents, or emulsifying agents. Further, these compounds may not only be applied alone or in mixtures with other compounds of the disclosed class, but may also be used in combination with other active toxicants in the formulation of fungicidal compositions.

The compounds may be applied to any environmental area which is a host to fungus or susceptible to fungus attack. For example, the fungicidal compositions may be sprayed or otherwise applied directly to a plant or other host, may be applied to the plant seed, sprayed upon the soil or other plant environment, or used in similar ways so as to effect the control of fungus and fungus diseases.

7 8 We claim: f 2. N (1 halo 1 nitroalkylthio) cis A tetra- 1. Compound of the formula hydrophthalimide wherein the alkyl group is of 2 to 6 carbon atoms. =1

3. N-(1-ha1o-1-nitroa1ky1thio)phthalimide whereinthe if 5 alkyl group is of 2 to 6 carbon atoms. 0 A/ \N-SB r References Cited 0 UNITED STATES PATENTS (i V 10 3,036,088 5/1962 Harris 260326 NICHOLAS s. RIZZO, Primary Eitaminer wherein A is a 1,2-cyclohexy1ene ring having 0 to 3 sites of olefinic unsaturation substituted with 0 to 1 chloro, NARCAVAGE AsslstamExammer bromo, nitro or lower alkyl and B is a l-halo-l-nitroalkyl Us CL group in which the halogen is of atomic number 17 to 35 15 and the alkyl is of from 2 to 6 'carbon atoms." 260-260, 309-5; 424 251"263 

